Activation of the fibrinolytic cascade early in pregnancy among women with spontaneous preterm birth.

Objective: To evaluate the association of early pregnancy concentrations of thrombin-antithrombin III complex with subsequent spontaneous preterm birth.

Methods: In a nested case-control study, thrombin-antithrombin III complex was measured in plasma before 20 weeks of gestation (mean 9.9 weeks) among women without chronic conditions, preeclampsia, or growth restriction. C-reactive protein and non-high-density lipoprotein cholesterol were also measured. Women with spontaneous preterm birth before 34 weeks of gestation (n=29) and 34 weeks to 36 weeks of gestation (n=72) were compared with women with term births occurring at or after 37 weeks (n=219). Polychotomous logistic regression was used to relate elevated thrombin-antithrombin III complex (greater than 5.5 ng/mL), dyslipidemia (non-high-density lipoprotein cholesterol greater than the 90th percentile), and inflammation (C-reactive protein at or above 8 micrograms/mL) to risk of spontaneous preterm birth subtypes.

Results: Women with spontaneous preterm birth compared with term births had elevated thrombin-antithrombin III complex (P=.02), and they were more likely to have a thrombin-antithrombin III complex greater than 5.5 ng/mL (P<.01). Women with thrombin-antithrombin III complex in the highest compared with lowest quartile had a 4.6-fold (95% confidence interval 1.3-15.8) increased risk for spontaneous preterm birth before 34 weeks of gestation, adjusted for body mass index, race, inflammation, dyslipidemia, and gestational age at sampling. There was a dose-response trend between thrombin-antithrombin III complex and spontaneous preterm birth before 34 weeks (P<.01) and 34 to 36 weeks (P=.03).

Conclusion: There is evidence of early pregnancy systemic fibrinolysis among women with spontaneous preterm birth before 34 weeks of gestation independent of inflammation and dyslipidemia, perhaps secondary to microvascular injury.

Level Of Evidence: II.